Artículos (Medicina)
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Artículo Increasing prevalence of psoriasis in Spain: A population-based study (2018-2022)(2024-11-18) Cayuela, Lucía; Pereyra-Rodríguez, José-Juan; Hernández Rodríguez, Juan Carlos; Rodríguez Fernández-Freire, Lourdes; Cayuela, Aurelio; Universidad de Sevilla. CTS1088: Enfermedades InmunomediadasObjectives: This study aimed to investigate the prevalence of psoriasis in Spain from 2018 to 2022 and analyze trends by sex and age groups. Methods: We used the Primary Care Clinical Database (BDCAP) to identify individuals coded with psoriasis (S91) during the study period. Population data for calculating rates was obtained from the Primary Care Information System (SIAP). Crude, age- and sex-specific, and standardized prevalence rates were calculated. Joinpoint analysis assessed annual percentage change (APC) in prevalence. Results: The estimated psoriasis prevalence in Spain in 2022 was 1.9%. Psoriasis prevalence increased substantially by 43.3% (from 692,317 to 991,832 cases) over the study period. We observed a clear increase in both crude and standardized prevalence rates for men (7.2% annual increase) and women (8.3% annual increase) throughout the study period. Men consistently had slightly higher prevalence rates than women. Prevalence increased with age, reaching a peak in the 70-74 age group for men and 60-64 for women, before declining in older age groups. Conclusions: This study revealed a concerning increase in psoriasis prevalence in Spain, independent of population aging. Increased disease awareness, improved diagnostics, and greater treatment seeking behavior are potential explanations. Further research is needed to explore the underlying causes of this rise and inform public health interventions.Artículo The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease(Elsevier, 2024-07) Younossi, Zobair M.; AlQahtani, Saleh A.; Funuyet Salas, Jesús; Romero Gómez, Manuel; Yilmaz, Yusuf; Keklikkiran, Caglayan; Lazarus, Jeffrey V.; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla: CTS: Unidad de Hepatología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI))Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and po tential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a surveyabout disease burden in NAFLD. Participants completed a 35 item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe,16% USA,18% Asia) and 778 competed CLDQ-NASH. Of the studygroup, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest inde pendent predictor of lower HRQL scores (beta from-5% to-8% of score range size, p<0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncom fortable with the term “fatty liver disease” with lower Emotional Health scores (all p<0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients’ self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers’ perception may not adequately reflect patients’ perspective and experience with the disease.Artículo Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study(Elsevier, 2024-04) Maldonado, Natalia; López Hernández, Inmaculada; García Montaner, Andrea; López-Cortes, Luis Eduardo; Martínez Pérez-Crespo, Pedro María; Retamar Gentil, Pilar; Rodríguez-Baño, Jesús; Pascual Hernández, Álvaro; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de MicrobiologíaBackground Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. Methods Ecolibloodisolatesfromamulticentrecross-sectionalstudyofpatientsolderthan14yearspresentingwithsepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ2 or Fisher’s exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. Findings We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0⋅0045). Median virulence score was higher in group 1 (median 25⋅0 [IQR 20⋅5–29⋅0) than in group 2 (median 14⋅5[9⋅0–20⋅0]; p<0⋅0001) and group 3 (median 21 [16⋅5–23⋅0]; p<0⋅0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29–35]) than the other predominant clones (median range 21–28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. Interpretation In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection.Artículo Current practice of screening and antimicrobial prophylaxis to prevent Gram-negative bacterial infection in high-risk haematology patients: results from a pan-European survey(Sage Publications Ltd, 2024-10-29) Stemler, Jannik; Gavriilaki, Eleni; Hlukhareva, Oksana; Khanna, Nina; Neofytos, Dionysios; Akova, Murat; Pagano, Livio; Cisneros, José Miguel; Cornely, Oliver A.; Salmanton-Garcia, Jon; Universidad de Sevilla. Departamento de MedicinaBackground: Bacterial infections frequently occur in haematological patients, especially during prolonged neutropenia after intensive chemotherapy, often leading to bloodstream infections and pneumonia. Objective: Routine antimicrobial prophylaxis (AMP) for high-risk haematology patients is still debated while prevalence of multi-drug resistant (MDR) Gram-negative bacteria (GNB) is rising globally. We aimed to assess the current practice of AMP in this population. Design: Cross-sectional observational survey study. Methods: Haematologists and infectious diseases physicians Europewide were invited to an online survey including questions on routine screening for GNB, incidence of MDR-GNB colonization, antimicrobial prophylaxis practices, rates of bloodstream infections (BSI), ICU admission and mortality differentiated by infections due to GNB versus MDR-GNB. Results: 120 haematology centres from 28 countries participated. Screening for MDR-GNB is performed in 86.7% of centres, mostly via rectal swabs (58.3%). In 39.2% of routine AMP is used, mostly with fluoroquinolones. Estimates of GNB-BSI yielded higher rates in patients not receiving anti-GNB prophylaxis than in those who do for E. coli (10% vs 7%) Klebsiella spp. (10% vs 5%), and Pseudomonas spp. (5% vs 4%). Rates for MDR-GNB infection were estimated lower in centres that administer AMP for MDR E. coli (5% vs 3%) Klebsiella spp. (5% vs 3%), and Pseudomonas spp. (2% vs 1%). In an exploratory analysis, Southern and Eastern European countries expected higher rates of MDR-GNB infections with lower ICU admission and mortality rates which may be subject to estimation bias. Conclusion: Screening for MDR-GNB is frequently performed. AMP against GNB infections is still often implemented. Estimated BSI rates are rather low, while the rate of MDR-GNB infections rises. Tailored prophylaxis including antimicrobial stewardship becomes more important.Artículo A phase III randomized controlled trial of plitidepsin, a marine-derived compound, in hospitalized adults with moderate covid-19(Oxford University Press, 2024-08-26) Landete, Pedro; Caliman-Sturdza, Olga Adriana; Lopez-Martin, Jose A.; Preotescu, Liliana; Luca, Mihaela-Catalina; Kotanidou, Anastasua; Cisneros, José Miguel; Varona, Jose Felipe; Universidad de Sevilla. Departamento de MedicinaBackground. Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. Methods. Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. Results. After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19–related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval, .96–1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73–1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. Conclusions. Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.Artículo Could the Adoptive Transfer of Memory Lymphocytes be an Alternative Treatment for Acinetobacter baumannii Infections?(MDPI, 2024-09-30) Cebrero-Cangueiro, Tania; Herrera-Espejo, Soraya; Paniagua, María; Labrador-Herrera, Gema; Cisneros, José Miguel; Universidad de Sevilla. Departamento de Medicina; Consejeria de Salud de la Junta de Andalucia; European Development Regional Fund "A way to achieve Europe"; Instituto de Salud Carlos III; Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious DiseasesWe evaluated the efficacy of the adoptive transfer of memory B, CD4+, and CD8+ T lymphocytes compared with sulbactam and tigecycline in an experimental murine pneumonia model by two multidrug-resistant Acinetobacter baumannii strains, colistin-susceptible AbCS01 and colistin-resistant AbCR17. Pharmacodynamically optimized antimicrobial dosages were administered for 72 h, and intravenous administration of 2 × 106 of each of the memory cells in a single dose 30 min post-infection. Bacterial lung and blood counts and mortality rates were analyzed. Results showed that a single dose of memory B or CD4+ T cells was as effective as sulbactam in terms of bacterial clearance from the lungs and blood compared with the untreated mice or the tigecycline-treated mice inoculated with the AbCS01 strain. In the pneumonia model by AbCR17, a single dose of memory B or CD4+ T cells also reduced the bacterial load in the lungs compared with both antibiotic groups and was more efficacious than tigecycline in terms of blood clearance. Regarding survival, the adoptive transfer of memory B or CD4+ T cells was as effective as three days of sulbactam treatment for both strains. These data suggest that adoptive memory cell transfer could be a new effective treatment of multidrug-resistant A. baumannii infections.Artículo Effects of age, period, and cohort on the incidence of psoriasis in Spain: a 30-year review (1990-2019)(Elsevier, 2024) Cayuela, Lucía; Pereyra-Rodríguez, José-Juan; Hernández-Rodríguez, Juan Carlos; Rodríguez Fernandez-Freire, L.; Cayuela, Aurelio; Universidad de Sevilla. Departamento de MedicinaAim This study aimed to investigate the effects of age, period, and cohort on the incidence of psoriasis in Spain from 1990 through 2019 using the Global Burden of Disease (GBD) database and age-period-cohort (A-P-C) analysis. Methods We conducted an ecological trend study to analyze the incidence rates of psoriasis in Spain from 1990 through 2019. Joinpoint Regression Program, Version 5.0.2 - May 2023; Surveillance Research Program, National Cancer Institute and National Cancer Institute A-P-C tools were used to identify trends and assess the effects of age, period, and cohort. Results From 1990 through 2019, an estimated 2.99 million cases of psoriasis were diagnosed in Spain, with a mean annual increase of 0.49%. Significant decreases in age-standardized incidence rates (ASIR) were reported for both sexes, with women consistently maintaining a slightly higher ASIR. Joinpoint analysis revealed multiple turning points in the downward trend, indicating periods of stabilization. A-P-C analysis demonstrated significant declines in both net (overall trend) and local drift (age-specific trends), indicating a broad decrease in the incidence of psoriasis across most age groups. While the risk of psoriasis increased with age, peaking in the 50–54 age group, it declined thereafter. Furthermore, the analysis revealed a continuous decline in risk from 1990 through 2019 for both sexes, with individuals born in the early 21st century exhibiting a significantly lower risk vs those born in the early 20th century. Conclusion This study observed a slight decline in the reported psoriasis ASIR in Spain, potentially due to reduced exposure to risk factors. However, limitations in data and the complexity of factors influencing the incidence of psoriasis require further research.Artículo Mitomycin C as an anti-persister strategy against klebsiella pneumoniae: toxicity and synergy studies(MDPI, 2024-08-28) Pacios, Olga; Herrera-Espejo, Soraya; Armán, Lucía; Ibarguren-Quiles, Clara; Blasco, Lucía; Bleriot, Inés; Cisneros, José Miguel; Pachón-Ibáñez, María Eugenia; Tomás, María; Universidad de Sevilla. Departamento de MedicinaThe combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.Artículo Patch test results to the Spanish baseline patch test series according to age groups: a multicentric prospective study from 2019 to 2023(Wiley, 2024-09-12) Pesqué, David; Planella‐Fontanillas, Nidia; Borrego, Leopoldo; Sanz‐Sánchez, Tatiana; Zaragoza‐Ninet, Violeta; Serra‐Baldrich, Esther; Pereyra-Rodríguez, José-Juan; Giménez‐Arnau, Ana María; Universidad de Sevilla. Departamento de MedicinaIntroduction Patch test results may be influenced by age-related factors. However, there is still discordant evidence between age and patch test results. Objectives We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group. Methods Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre-defined as children (0- to 11-years), adolescents (12- to 18-years), young adults (19- to 30-years), middle-aged adults (31- to 65-years) and older adults (≥66-years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression. Results A total of 13 368 patients were patch-tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle-aged adults. Age-related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2-hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31–65 (OR: 1.41, 95% CI: 1.26–1.58) and above 66-years (OR: 1.15, 95% CI: 1.01–1.32) with a higher proportion of positive results, compared with young adults. Conclusions Positive patch test results vary according to age, with the highest occurrence in middle-aged adults. Most haptens did not present age-related differences, reinforcing the use of baseline series regardless of age.
Artículo Patterns and trends in melanoma mortality in Spain (1999–2022)(Springer, 2024-10-05) Cayuela, Lucía; Hernández-Rodríguez, Juan Carlos; Pereyra-Rodríguez, José-Juan; Sendín-Martín, Mercedes; Cayuela, Aurelio; Universidad de Sevilla. Departamento de MedicinaAim To examine melanoma mortality trends in Spanish Autonomous Communities from 1999 to 2022, focusing on gender and age differences. Methods Data from the National Statistics Institute were used to calculate age-standardized mortality rates (ASMRs). Joinpoint regression identified trend changes. Results Melanoma mortality varied significantly by region, gender, and age. Eastern Spain had higher male mortality, while western regions had lower rates. Asturias had higher female mortality, with lower rates in Andalusia, Extremadura, and Castilla-La Mancha. Men generally exhibited higher ASMRs than women, with variations across regions. While ASMRs remained stable in most areas, Madrid experienced a notable decline (AAPC: − 1.3%). A national trend reversal occurred in 2014 (AAPC: − 1.3%). For individuals aged 45–74 years, Catalonia saw a significant decrease (AAPC: − 1.1%, p < 0.05), whereas Andalusia experienced an increase (APC: 2.1% since 2007). Nationally, ASMRs for this age group declined (AAPC: − 0.7%). Among those aged 75 years and over, ASMRs varied considerably, with increases observed in Andalusia and Aragon. Nationally, male ASMRs rose (AAPC: 1.6% per year), while female rates were stable. Regional disparities were evident, with higher female mortality in the Balearic Islands and fluctuating rates in the Community of Madrid (an increase followed by a decrease after 2015). The gender gap in mortality varied across regions, with some areas showing a narrowing gap and others widening disparities. Conclusion Continuous monitoring of melanoma mortality, especially among men and older adults, is crucial. Public health efforts should address regional disparities, improve early detection, and enhance treatment access to optimize outcomes nationwide.Artículo Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of ['Escherichia coli', 'Klebsiella pneumoniae'] and(MDPI, 2024-09-01) Herrera Espejo, Soraya; Carretero Ledesma, Marta; Bahamonde-Garcia, Manuel Anselmo; Cordero Matia, María Elisa; Pachón Díaz, Jerónimo; Pachón Ibáñez, María Eugenia; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos III, Spain; Subdireccion General de Evaluacion y Fomento de la Investigacion, Ministerio de Economia, Industria y CompetitividadIn vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals’ immunocompetence status.Artículo Integrating the Tumor Microenvironment into Cancer Therapy(Mdpi, 2020-06-24) Sanegre, Sabina; Lucantoni, Federico; Burgos-Panadero, Rebeca; Cruz Merino, Luis de la; Universidad de Sevilla. Departamento de Medicina; Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Universidad de Sevilla. CTS151: Bioquímica médica.Tumor progression is mediated by reciprocal interaction between tumor cells and their surrounding tumor microenvironment (TME), which among other factors encompasses the extracellular milieu, immune cells, fibroblasts, and the vascular system. However, the complexity of cancer goes beyond the local interaction of tumor cells with their microenvironment. We are on the path to understanding cancer from a systemic viewpoint where the host macroenvironment also plays a crucial role in determining tumor progression. Indeed, growing evidence is emerging on the impact of the gut microbiota, metabolism, biomechanics, and the neuroimmunological axis on cancer. Thus, external factors capable of influencing the entire body system, such as emotional stress, surgery, or psychosocial factors, must be taken into consideration for enhanced management and treatment of cancer patients. In this article, we review prognostic and predictive biomarkers, as well as their potential evaluation and quantitative analysis. Our overarching aim is to open up new fields of study and intervention possibilities, within the framework of an integral vision of cancer as a functional tissue with the capacity to respond to different non-cytotoxic factors, hormonal, immunological, and mechanical forces, and others inducing stroma and tumor reprogramming.Artículo Survival of infection with TEM beta-lactamase-producing Escherichia coli with Pan-beta-lactam resistance(Elsevier, 2024) Rodriguez-Villodres, Angel; Ortiz de la Rosa, Jose Manuel; Galvez-Benitez, Lydia; Gascon, Maria Luisa; Penalva, German; Dorado Pardo, Francisco J.; Cisneros, José Miguel; Lepe Jiménez, José Antonio; Universidad de Sevilla. Departamento de Microbiología; Universidad de Sevilla. Departamento de MedicinaBackground: Antimicrobial resistance is a critical global health issue, significantly contributing to patient mortality. Recent antibiotic developments have aimed to counteract carbapenemase-producing Enterobacterales; however, the impact of their use on the emergence of antibiotic resistance is unknown. This study investigates the first case of a non-carbapenemase-producing, pan-β-lactam-resistant Escherichia coli strain from a patient previously treated with ceftolozane-tazobactam and cefiderocol. Methods: This study describes the clinical progression of a 39-year-old ICU patient who developed multiple infections, culminating in the isolation of a pan-β-lactam-resistant E. coli strain (EC554). The resistance profile was characterised through MIC determination, whole-genome sequencing, the use of the β-lactam inactivation method, RT-qPCR, efflux pump inhibition assays, outer membrane protein analysis, and blaTEM transformation. Findings: The EC554 isolate displayed resistance to all tested β-lactams and β-lactam-β-lactamase inhibitor combinations. Whole-genome sequencing revealed four plasmids in EC554, with the only β-lactamase gene being blaTEM-252 on the pEC554-PBR-X1-X1 plasmid. We found that the extremely resistant phenotype was attributable to a combination of different mechanisms: a high expression of TEM-252, efflux pump activity, porin loss, and PBP3 mutations. Interpretation: The findings illustrate the complex interplay of multiple resistance mechanisms in E. coli, highlighting the potential for high-level resistance even without carbapenemase production. This study underscores the importance of comprehensively characterising resistance mechanisms in order to inform effective treatment strategies and mitigate the spread of resistant strains.Artículo FIB-4 score as predictor of COVID-19-related severity in hospitalized patients(Arán Ediciones, S.L., 2024) Lucena Valera, Ana; Aller Dela Fuente, Rocio; Sanchez Torrijos, Yolanda; Romero Gómez, Manuel; Ampuero Herrojo, Javier; Universidad de Sevilla. Departamento de Medicina; Carlos III Health Institute; Health Department of the Autonomous Government of Andalusia; Spanish Ministry of Economy, Innovation and CompetitionAim: to determine the impact of liver fibrosis on the prognosis of COVID and liver injury associated with the infection. Methods: retrospective multicenter study including 575 patients requiring admission for COVID-19 between January and June 2020. Fibrosis index-4 (FIB-4) was calculated within six months prior to infection and at six months post-infection. Results: baseline FIB-4 was elevated in patients who died (1.91 ± 0.95 vs 1.43 ± 0.85; p < 0.001). In addition, 17.1 % (32/187) of patients with baseline FIB-4 < 1.45 died vs 52.9 % (9/17) with FIB-4 > 3.25 (p < 0.001). In the adjusted multivariate analysis, baseline FIB-4 (OR 1.61 [95 % CI: 1.19-2.18]; p = 0.002) was independently associated with mortality. Parameters associated with liver injury, including aspartate aminotransferase (AST) (28 ± 10 vs 45 ± 56 IU/l; p < 0.001) and alanine aminotransferase (ALT) (20 ± 12 vs 38 ± 48 IU/l; p < 0.001) were significantly higher at admission compared to baseline. Furthermore, FIB-4 increased from baseline to the time of admission (1.53 ± 0.88 vs 2.55 ± 1.91; p < 0.001), and up to 6.9 % (10/145) of patients with FIB-4 < 1.45 on admission died vs 47.5 % if FIB-4 > 3.25 (58/122) (p < 0.001). In the adjusted multivariate analysis, FIB-4 on admission (OR 1.14 [95 % CI: 1.03-1.27]; p = 0.015) was independently associated with mortality. In addition, AST (42 ± 38 vs 22 ± 17 IU/l; p < 0.001) and ALT (40 ± 50 vs 20 ± 19 IU/l; p < 0.001) were significantly reduced at six months after the resolution of infection. Accordingly, FIB-4 decreased significantly (2.12 ± 1.25 vs 1.32 ± 0.57; p < 0.001) six months after the infection. Conclusion: increased FIB-4, either at baseline or at the time of admission, was associated with severity and mortality related to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the liver damage expressed by elevated transaminases and FIB-4 levels was reversible in most of patients.Artículo Vedolizumab and ART in recent HIV-1 infection unveil the role of α4β7 in reservoir size(American Society for Clinical Investigation, 2024-08-22) Jimenez-Leon, Maria Reyes; Gasca-Capote, Carmen; Roca-Oporto, Cristina; Espinosa, Nuria; Sobrino, Salvador; Fontillon-Alberdi, Maria; Cervera Barajas, Antonio; Bachiller, Sara; López Cortés, Luis Fernando; Ruiz-Mateos, Ezequiel; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Conocimiento, Empresas y Universidad; Conserjeria de Economia; Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe,"; Junta de Andalucia; Red Tematica de Investigacion Cooperativa en SIDA; Spanish National Research CouncilBACKGROUNDWe evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of α4β7 on the HIV-1 reservoir size.METHODSParticipants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed.RESULTSVedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, α4β7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4β7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4β7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4β7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4β7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe," research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council.Artículo Effects of pH on the pathogenicity of escherichia coli and klebsiella pneumoniae on the kidney: in vitro and in vivo studies(MDPI, 2024-07-19) Herrera Espejo, Soraya; Dominguez-Miranda, Jose Luis; Rodriguez-Mogollo, Juan Ignacio; Pachón Díaz, Jerónimo; Cordero Matia, María Elisa; Pachón Ibáñez, María Eugenia; Universidad de Sevilla. Departamento de Medicina; Instituto de Salud Carlos III; Instituto de Salud Carlos III, Spain; the Subdireccion General de Evaluacion y Fomento de la Investigacion, Ministerio de Economia, Industria y CompetitividadUrine pH reflects the functional integrity of the body and may influence the virulence of uropathogenic Escherichia coli and Klebsiella pneumoniae, the main causes of urinary tract infections (UTIs). This study evaluated the effects of acidic pH on the pathogenicity of uropathogenic E. coli and K. pneumoniae strains, in vitro and in vivo. Four uropathogenic E. coli and four K. pneumoniae strains were used. Biofilm formation, growth competition indices, motility, and adhesion and invasion of human renal cells were analyzed in media with acidic, neutral, and alkaline pH. A murine lower UTI model was used, with urine adjusted to acidic, neutral, or alkaline pH. At acidic pH, E. coli and K. pneumoniae exhibited higher bacterial concentrations in the kidneys and systemic symptoms, including bacteremia. Alkaline urine pH did not affect bacterial concentrations of any strain. In mice with UTIs caused by E. coli Nu14 and K. pneumoniae HUVR42 and acidic urine pH, histopathological studies of the kidneys showed acute inflammation affecting the urothelium and renal parenchyma, which are traits of acute pyelonephritis. These results indicate that acidic pH could increase the pathogenicity of E. coli and K. pneumoniae in murine models of lower UTI, promoting renal infection and acute inflammation.Artículo Melanoma Breslow thickness classification using ensemble-based knowledge distillation with semi-supervised convolutional neural networks(EEE-Inst Electrical Electronics Engineers Inc, 2024-09-20) Domínguez Morales, Juan Pedro; Hernández Rodríguez, Juan Carlos; Durán López, Lourdes; Conejo-Mir Sánchez, Julián; Pereyra-Rodríguez, José-Juan; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Arquitectura y Tecnología de ComputadoresMelanoma is considered a global public health challenge and is responsible for more than 90% deaths related to skin cancer. Although the diagnosis of early melanoma is the main goal of dermoscopy, the dis crimination between dermoscopic images of in situ and invasive melanomas can be a difficult task even for expe rienced dermatologists. Recent advances in artificial intel ligence in the field of medical image analysis show that its application to dermoscopy with the aim of supporting and providing a second opinion to the medical expert could be of great interest. In this work, four datasets from different sources were used to train and evaluate deep learning models on in situ versus invasive melanoma classification and on Breslow thickness prediction. Supervised learning and semi-supervised learning using a multi-teacher ensem ble knowledge distillation approach were considered and evaluated using a stratified 5-fold cross-validation scheme. The best models achieved AUCs of 0.8085±0.0242 and of 0.8232±0.0666 on the former and latter classification tasks, respectively. The best results were obtained using semi supervised learning, with the best model achieving 0.8547 and 0.8768 AUC, respectively. An external test set was also evaluated, where semi-supervision achieved higher performance in all the classification tasks. The results ob tained show that semi-supervised learning could improve the performance of trained models in different melanoma classification tasks compared to supervised learning. Au tomatic deep learning-based diagnosis systems could sup port medical professionals in their decision, serving as a second opinion or as a triage tool for medical centers.Artículo Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update(Elsevier, 2024-08-05) Ruiz-Arabi, Elisa; Torre-Cisneros, Julián; Aguilera, Victoria; Alonso, Rodrigo; Berenguer, Marina; Bestard, Oriol; Cordero Matia, María Elisa; Sánchez Céspedes, Javier; Aguado, José María; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. CTS 203: Estudio de las Enfermedades InfecciosasCytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.Artículo Mapping the human genetic architecture of COVID-19(Nature Research, 2021-07-08) Romero Gómez, Manuel; Calderón Sandubete, Enrique José; Medrano Ortega, Francisco Javier; Morilla Romero de la Osa, Rubén; Ampuero Herrojo, Javier; Delgado de la Cuesta, Juan; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; NIMH NIH HHSThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Artículo Genetic Polymorphisms of Superoxide Dismutase Locus of Pneumocystis jirovecii in Spanish Population(Frontiers Media, 2019-10-15) Morilla Romero de la Osa, Rubén; González-Magaña, Amaia; Friaza, Vicente; Armas, Yaxsier de; Medrano Ortega, Francisco Javier; Calderón Sandubete, Enrique José; Horra Padilla, Carmen de la; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; The Ibero-American Programme for Science, Technology and DevelopmentObjective: Pneumocystis pneumonia remains a major opportunistic infection in immunocompromised patients worldwide. Colonization with Pneumocystis jirovecii has recently gained attention as an important issue for understanding the complete cycle of human Pneumocystis infection. P. jirovecii Superoxide Dismutase (SOD) gene could be a molecular target with high clinical relevance, but the epidemiological information about SOD genotypes distribution is scarce. The aim of this work was to provide information about the prevalence of genotypes of Pneumocystis SOD among Spanish patients and to describe possible differences between colonized and Pneumocystis pneumonia patients. Methods: we developed a cross-sectional study analyzing broncho-alveolar lavage fluid samples from 30 Pneumocystis pneumonia patients, 30 colonized patients, and 20 controls using a nested PCR protocol designed to amplify the sodA gene of P. jirovecii. The diagnostic yield of SOD Nested PCR was evaluated against the routine practice of mtLSUrRNA Nested PCR, which is considered the gold standard. Results: SOD locus was amplified in 90% of Pneumocystis pneumonia patients, 10% of colonized patients, and none of controls. Genotype SOD1 was observed in 11 cases (52.4%) and genotype SOD2 in 10 cases (47.6%). Genotype SOD2 was observed only in Pneumocystis pneumonia patients while the genotype SOD1 was observed in both colonized and Pneumocystis pneumonia patients. Conclusions: This study provides epidemiological information about SOD genotypes distribution in Spain, showing a low genetic diversity and a predominant presence of genotype SOD1 in colonized patients. SOP Nested PCR was more sensitive and accurate assay in Pneumocystis pneumonia patients than in colonized individuals.